AXIOS Stent and Electrocautery-Enhanced Delivery System (10mm x 10mm Stent); AXIOS Stent and Electrocautery-Enhanced Delivery System (15mm x 10mm Stent)

Q: Who is the manufacturer of AXIOS Stent and Electrocautery-Enhanced Delivery System (10mm x 10mm Stent); AXIOS Stent and Electrocautery-Enhanced Delivery System (15mm x 10mm Stent)?

Boston Scientific Corporation filed the De Novo classification request for AXIOS Stent and Electrocautery-Enhanced Delivery System (10mm x 10mm Stent); AXIOS Stent and Electrocautery-Enhanced Delivery System (15mm x 10mm Stent) (DEN230019).

Q: What is the FDA product code for AXIOS Stent and Electrocautery-Enhanced Delivery System (10mm x 10mm Stent); AXIOS Stent and Electrocautery-Enhanced Delivery System (15mm x 10mm Stent)?

QXH. It is classified under 21 CFR 876.5016 as a Class 2 device in the Gastroenterology, Urology panel.

Q: What is the regulatory pathway for AXIOS Stent and Electrocautery-Enhanced Delivery System (10mm x 10mm Stent); AXIOS Stent and Electrocautery-Enhanced Delivery System (15mm x 10mm Stent)?

De Novo classification (submission type: Direct).

Q: Who can help prepare an FDA De Novo submission like AXIOS Stent and Electrocautery-Enhanced Delivery System (10mm x 10mm Stent); AXIOS Stent and Electrocautery-Enhanced Delivery System (15mm x 10mm Stent)?

Innolitics — a medical-device software consultancy — provides regulatory and engineering support for FDA De Novo submissions. See https://innolitics.com/services/regulatory/ or contact https://innolitics.com/contact.

DEN230019 · Boston Scientific Corporation · QXH · Aug 18, 2023 · Gastroenterology, Urology

Device Facts

Record ID	DEN230019
Device Name	AXIOS Stent and Electrocautery-Enhanced Delivery System (10mm x 10mm Stent); AXIOS Stent and Electrocautery-Enhanced Delivery System (15mm x 10mm Stent)
Applicant	Boston Scientific Corporation
Product Code	QXH · Gastroenterology, Urology
Decision Date	Aug 18, 2023
Decision	DENG
Submission Type	Direct
Regulation	21 CFR 876.5016
Device Class	Class 2
Attributes	Therapeutic

Indications for Use

The AXIOS Stent and Electrocautery Enhanced Delivery System is indicated for use to facilitate transgastric or transquodenal endoscopic drainage of the gallbladder in patients with acute cholecystitis who are at high risk for surgery.

Device Story

Device facilitates endoscopic gallbladder drainage via transgastric or transduodenal approach; consists of fully covered, self-expanding, braided nitinol stent with silicone covering and electrocautery-enhanced delivery system. Stent features two flanges for tissue apposition and migration prevention; delivery system includes catheter and handle with manual controls for deployment. Used in gastrointestinal tract with echoendoscopes (≥3.7 mm working channel) and insulated guidewires; connects to standard electrosurgical units. Physician performs procedure under endoscopic ultrasound guidance. Stent creates fistula between gallbladder and stomach/duodenum to drain contents; removed after 30-60 days. Benefits include symptom resolution in high-surgical-risk patients; reduced adverse events compared to percutaneous cholecystostomy.

Clinical Evidence

Clinical performance data required to demonstrate intended performance, including stent patency, placement, and removal. Data must capture adverse events observed during clinical use.

Technological Characteristics

Stent and delivery system; includes electrocautery capability. Requires biocompatibility, sterility, and MR compatibility evaluation. Performance testing includes deployment, removal force, compression/expansion force, dimensional verification, tensile testing, fatigue, and corrosion testing.

Indications for Use

Indicated for transgastric or transduodenal endoscopic gallbladder drainage in patients with acute cholecystitis who are at high risk for surgery.

Regulatory Classification

Identification

The AXIOS Stent and Electrocautery-Enhanced Delivery System is a prescription device intended to facilitate transgastric or transduodenal endoscopic drainage of the gallbladder in patients with acute cholecystitis who are at high risk for surgery. The system consists of a flexible, magnetic resonance conditional, fully covered, self-expanding, braided nitinol stent with two flanges and a silicone covering, preloaded into an electrocautery-enhanced delivery system with an integrated handle for positioning and deployment.

Special Controls

In combination with the general controls of the FD&C Act, the gallbladder drainage stent and delivery system is subject to the following special controls:

Related Devices

K252648 — Niti-S SPAXUS Stent · Taewoong Medical Co., Ltd. · Mar 13, 2026
K181905 — AXIOS Stent and Delivery System, AXIOS Stent and Electrocautery Enhanced Delivery System · Boston Scientific Corporation · Mar 25, 2019
K163272 — AXIOS Stent and Electrocautery Enhanced Delivery System · Boston Scientific Corporation · Feb 18, 2017
K203132 — AXIOS Stent and Electrocautery Enhanced Delivery System · Boston Scientific Corporation · Apr 15, 2021

Submission Summary (Full Text)

{0}------------------------------------------------ # DE NOVO CLASSIFICATION REQUEST FOR AXIOS STENT AND ELECTROCAUTERY-ENHANCED DELIVERY SYSTEM (10 MM X 10 MM STENT); AXIOS STENT AND ELECTROCAUTERY-ENHANCED DELIVERY SYSTEM (15 MM X 10 MM STENT) #### REGULATORY INFORMATION FDA identifies this generic type of device as: Gallbladder drainage stent and delivery system. A gallbladder drainage stent is a prescription device intended to facilitate transgastric or transduodenal endoscopic drainage of the gallbladder. This device may also include a delivery system. NEW REGULATION NUMBER: 21 CFR 876.5016 CLASSIFICATION: Class II PRODUCT CODE: QXH #### BACKGROUND DEVICE NAME: AXIOS Stent and Electrocautery-Enhanced Delivery System (10 mm x 10 mm Stent); AXIOS Stent and Electrocautery-Enhanced Delivery System (15 mm x 10 mm Stent) SUBMISSION NUMBER: DEN230019 DATE DE NOVO RECEIVED: March 27, 2023 #### SPONSOR INFORMATION: Boston Scientific Corporation 100 Boston Scientific Way Marlborough, Massachusetts 01752 #### INDICATIONS FOR USE The AXIOS Stent and Electrocautery-Enhanced Delivery System (10 mm x 10 mm Stent); AXIOS Stent and Electrocautery-Enhanced Delivery System (15 mm x 10 mm Stent) is indicated as follows: The AXIOS Stent and Electrocautery Enhanced Delivery System is indicated for use to facilitate transgastric or transquodenal endoscopic drainage of the gallbladder in patients with acute cholecystitis who are at high risk for surgery. #### LIMITATIONS {1}------------------------------------------------ The sale, distribution, and use of the AXIOS Stent and Electrocautery-Enhanced Delivery System (10 mm x 10 mm Stent); AXIOS Stent and Electrocautery-Enhanced Delivery System (15 mm x 10 mm Stent are restricted to prescription use in accordance with 21 CFR 801.109. Placement of the AXIOS Stent should be performed by physicians familiar with endoscopic ultrasonography and who have received training for AXIOS Stent placement techniques. PLEASE REFER TO THE LABELING FOR A COMPLETE LIST OF WARNINGS. PRECAUTIONS AND CONTRAINDICATIONS. ## DEVICE DESCRIPTION The AXIOS Stent and Electrocautery-Enhanced Delivery system is designed to help facilitate the transgastric or transduodenal endoscopic drainage of the gallbladder. The AXIOS Stent remains identical to the stents cleared previously per K220112. The AXIOS Stent is a flexible, magnetic resonance conditional, fully covered, self-expanding, braided nitinol stent, which comes preloaded into the delivery system. The AXIOS stent is designed with two flanges, one on each end, to prevent migration and to enable tissue plane apposition and a "saddle" in between the flanges to span the tissue implant distance (Figure 1), The stent is fully covered with silicone to prevent leakage, discourage tissue in-growth within the nitinol woven braid, and facilitate removal. Image /page/1/Figure/6 description: The image shows two views of a medical stent labeled as "Figure 1: AXIOS(TM) Stent". On the left, the stent is viewed from the side, showing its hourglass shape with labels indicating "Flange Diameter", "Saddle Length", and "Lumen Diameter". On the right, the stent is viewed head-on, revealing its circular structure and the "Drainage Lumen" in the center. Figure 1: AXIOS M Stent {2}------------------------------------------------ | Description | Stent Size | | | Delivery | |-----------------------------------------------------------------------------------|-------------------|------------------|--------------------|-----------------------------| | | Lumen Diameter | Saddle Length | Flange Diameter | System Outer Diameter | | AXIOS Stent and Electrocautery-Enhanced Delivery System (10mm x 10mm Stent) | 10 mm | 10 mm | 21 mm | 10.8 Fr | | AXIOS Stent and Electrocautery-Enhanced Delivery System (15mm x 10mm Stent) | 15 mm | 10 mm | 24 mm | 10.8 Fr | The following stent sizes are included in this submission: The AXIOS Electrocautery-Enhanced Delivery System consists of a catheter and an integrated handle with manual controls for positioning and deploying the AXIOS™ Stent. The AXIOS™ Electrocautery-Enhanced Delivery System is designed to be used in the gastrointestinal tract with commercially available echoendoscopes with a 3.7 mm diameter or larger working chamel and is compatible with commercially available 0.035-inch insulated endoscopic guidewires. The Electrocautery-Enhanced Delivery System connects with an off-the-shelf electrosurgical unit or generator that is compliant to IEC 60601-1-2 and IEC 60601-2-2. Image /page/2/Figure/4 description: The image shows a medical device with several labeled parts. The device includes components such as a 'Luer Lock,' 'Catheter Lock,' 'Stent Lock,' 'Safety Clip,' and 'Monopolar Plug.' The labels point to specific areas of the device, providing a clear understanding of its structure and function. Figure 2: Electrocantery Enhanced AXIOS Delivery System Handle {3}------------------------------------------------ Image /page/3/Picture/0 description: The image shows a medical device, possibly an endoscope or a similar instrument used for minimally invasive procedures. The device has a long, flexible tube extending from a handle with controls. The handle appears to have a grip and adjustment mechanisms, suggesting it is used to manipulate the distal end of the tube for navigation and operation within the body. Figure 3: Electrocantery Enhanced AXIOSTM Delivery System # SUMMARY OF NONCLINICAL/BENCH STUDIES The performance of the AXIOS Stent and Delivery System was evaluated using the testing described in Table 1 below. | Test | Purpose | Method | Acceptance Criteria | Results | |-------------------------------------------------------------------|-----------------------------------------------------------------------------------------------|------------------------------------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------| | Deployed Stent Saddle Length | Verify dimensions of deployed stent | Measure deployed stent | Deployed Stent Saddle Length (inside flange to inside flange) @37°C $\geq$ 8.5 mm ≤ 13 mm For both the AXIOS 10 mm x 10 mm AXIOS 15 mm x 10 mm | Pass | | Deployed Stent Saddle Outer Diameter | Verify dimensions of deployed stent | Measure deployed stent | Deployed Stent Saddle Outer Diameter @37°C AXIOS 10mm x 10 mm stent: $\geq$ 8 mm | Pass | | Test | Purpose | Method | Acceptance Criteria | Results | | | | | AXIOS 15mm x 10mm stent: ≥ 13 mm | | | Deployed Stent Flange Width | Verify dimensions of deployed stent | Measure deployed stent | Deployed Flange Width @ 37°C AXIOS 10 mm x 10 mm: ≥ 3 mm AXIOS 15 mm x 10 mm: ≥ 3 mm | Pass | | Stent Pull-Out Force | Verify stent will remain in place when pull-out force is applied | Deploy stent into test fixture. Pull stent until either stent flange slips through orifice. | AXIOS 10 mm x 10 mm: ≥ 2.54 N | Pass | | Stent (Saddle) Radial Strength – Compression & Expansion | Verify expansion strength of the compressed stent meets product specification | Compress stent using force gauge. Measure force at 50% reduction of original stent diameter. | AXIOS 10mm x 10 mm and 15 mm x10 mm: Stent (Saddle) Radial Strength – in compression @ 37°C ≥ 0.06 N/mm of length @ 50% Ø. AXIOS 10 mm x 10 mm and 15 mm x 10 mm: Stent (Saddle) Radial Strength – in expansion @ 37°C ≥ 0.02 N/mm of length @ 50% Ø. | Pass | | Deployment (Unsheathing) Force | Verify force needed to deploy stent | Measure deployment force of stent using force gauge. | AXIOS 10 mm x 10 mm: Stent Deployment Force ≤ 40 N (AXIOS) 15 mm x 10 mm stent: Stent Deployment Force ≤ 40 N | Pass | | Implant Anchor Function – Retention (Tensile) | Verify force needed to achieve apposition of distal flange to target structure | Measure force to pull stent through simulated test fixture | AXIOS 10 mm x 10 mm: ≥ 2 N (AXIOS) 15 mm x 10 mm stent ≥ 2 N | Pass | | Magnetic Resonance Testing | Verify stent will not prevent ability to use MRI | Testing per ASTM F2182, ASTM 2119, | The stent should not prevent the ability of the physician to use | Pass | | Test | Purpose | Method | Acceptance Criteria | Results | | | | ASTM F2052, ASTM F2213, ASTM F2503 | Magnetic Resonance Imaging on the patient | | | Fatigue Testing | Ensure stent remains intact throughout the period of use | Test stents in fatigue tester with off-axis displacement of 2 mm | The stent must remain intact after 940,000 translation (distal flange with respect to proximal flange) cycles. | Pass | | Corrosion Testing | Evaluate corrosion resistance of stent | Test in accordance with ASTM F2129 | The metal stent and stent covering must show corrosion resistance when subjected to an in vitro corrosive environment equivalent to sixty days | Pass | | Delivery System Working Length | Verify working length of delivery device | Measure length of device | Working Length (distal point of the handle to distal end of the catheter tip) ≤ 138 cm | Pass | | Slider lock hold force testing | Evaluate performance of lock under compressional and torsional forces | Measure displacement of catheter after applying 5 lbf of compression/ten sion to locked proximal hub | Lock hold force ≥ 22 N | Pass | | Nose lock hold force | Evaluate performance of lock under compressional and torsional forces | Measure displacement of catheter after applying 5 lbf of compression/ten sion to locked proximal hub | Lock hold force ≥ 22 N | Pass | | Nose/slide lock cycling | Inspect function of nose/slide lock feature | Lock and unlock nose/slide lock for a predetermined number of cycles | Nose lock must function after 6 cycles; slide lock must function after 4 cycles | Pass | | Joint Strength Testing | Verify joint strength meets design requirements | Test methods per EN ISO 10555-1 | Per EN ISO 10555-1, the device shall meet specific minimum force | Pass | | Luer to Nose Joint Strength | Verify peak tensile force of luer to nose joint | Load delivery system into test | Luer to Nose Joint Strength ≥ 22 N | Pass | | Test | Purpose | Method | Acceptance Criteria | Results | | | | setup and apply force until luer to nose joint fails. Record peak force. | | | | Outer Sheath to Handle Torque Strength | Verify ability of AXIOS catheter to withstand torque when the device is rotated 360° | Rotate device handle 360 degrees clockwise while holding proximal end of handle assembly. | The catheter system must withstand a minimum of 1 full turn. | Pass | | Tracking Force | Verify tracking force of outer sheath through a 3.7 mm working channel | Load catheter into stomach model and measure force when tip of sheath exits model | Track force $≤$ 8.83 N | Pass | Table 1. Performance Testing for AXIOS Stent and Delivery System {4}------------------------------------------------ {5}------------------------------------------------ {6}------------------------------------------------ ## BIOCOMPATIBILITY/MATERIALS The AXIOS Stent is defined as an implanted, tissue/bone contacting device with a contact duration greater than 30 days. Biocompatibility was evaluated in accordance with ISO 10993-1, Biological evaluation of medical devices and FDA Guidance: Use of International Standard 1SO 10993-1, "Biological evaluation of medical devices - Part 1: Evaluation and testing within a risk management process." The following biocompatibility endpoints were evaluated: - Cytotoxicity . - Sensitization . - Irritation . - Acute Systemic Toxicity . - Genotoxicity . - . Implantation The AXIOS Delivery Device is defined as an externally communicating, tissue/bone contacting device with a contact duration less than 24 hours. The following biocompatibility endpoints were evaluated: - . Cytotoxicity - Sensitization . - Intracutaneous reactivity . - Material mediated pyrogenicity . - . Acute systemic toxicity The provided biocompatibility data help demonstrate the biocompatibility of the device. {7}------------------------------------------------ ## SHELF LIFE/STERILITY The AXIOS Stent and Delivery System are single use devices that are sterilized with ethylene oxide. The sterilization methods, location, and packaging integrity information are the same as referenced in K220112 and K192043. Sterilization data on a new, alternative sterilization cycle was also provided. The new sterilization method was found acceptable. #### SUMMARY OF CLINICAL INFORMATION Clinical data from a single-arm pivotal study (from G170190) and data from literature sources were leveraged to help evaluate the safety and effectiveness of the AXIOS Stent and Delivery System. #### PIVOTAL STUDY DATA In the pivotal study (A Multicenter, Prospective Study of (endoscopic ultrasound) EUS-Guided Transluminal Gallbladder Drainage in Patients with Acute Cholecystitis as an Alternative to Percutaneous Gallbladder Drainage), thirty subjects who are at high risk or unsuitable for surgery were enrolled with grade I or II Acute Cholecystitis received an AXIOS stent for drainage of the gallbladder as an alternative to percutaneous cholecystostomy. The AXIOS stent was removed between 30 and 60 days unless AXIOS stent removal was not medically indicated. #### Primary Effectiveness Endpoints - . Symptom resolution: - o temperature < 100.5ºF - o 4-point decrease in pain score or - o white blood cell <12.000 cc with improvement in at least two categories without deterioration in the third category Secondary Effectiveness Endpoints - . Reintervention, migration, or occlusion #### Additional Endpoints - AXIOS stent placement: successful stent placement with confirmed stent patency . - AXIOS stent removal: successful endoscopic stent removal without stent removal-related . serious adverse events (SAE)s - Stent patency at stent removal visit . - Recurrence of acute cholecystitis symptoms . - . Reintervention visit - 72-hour post-stent removal visit . - Final study visit . - Days hospitalized (between index procedure and stent removal visit / end of study) . {8}------------------------------------------------ Table 2. Subject Demographics | Variable | ITT Patients (N=30) | |-------------|------------------------------------| | Age (yr) | $75.2\pm14.1(30)$ (34.0,94.0) | | Female | 36.7% (11/30) | | Male | 63.3% (19/30) | | Weight (kg) | $76.4\pm17.8(30)$ (43.4,120.0) | | Height (cm) | $168.6\pm9.4(30)$ (147.0,182.9) | | BMI (kg/m²) | $26.9\pm6.3(30)$ (18.2,44.1) | Above numbers are mean + standard deviation (min, max). | Variable | ITT Patients (N=30) | |-------------------------------------------|------------------------| | Ethnicity | | | Hispanic or Latino | 0.0% (0/30) | | Not Hispanic or Latino | 100.0% (30/30) | | Not disclosed | 0.0% (0/30) | | Race | | | American Indian or Alaskan native | 0.0% (0/30) | | Asian | 0.0% (0/30) | | Black or African American | 0.0% (0/30) | | Hispanic or Latino | 0.0% (0/30) | | Native Hawaiian or other pacific islander | 0.0% (0/30) | | White (Caucasian) | 100.0% (30/30) | | Not disclosed | 0.0% (0/30) | Study results are presented in Table 3 below. The endpoints are presented for the intent to treat (ITT) cohort (N=30), and for the treated and per protocol (PP) cohorts (N=28), which contained the same patients. {9}------------------------------------------------ | Variable | ITT Patients (N=30) | Treated/PP Patients (N=28) | |-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|------------------------------------------------------|---------------------------------------------------| | Primary Effectiveness Endpoint | | | | Symptom resolution: temp <100.5°F, 4-point decrease in pain score or WBC<12,000 cc with improvement in at least 2 categories without deterioration in the third category | | | | Primary Analysis: Patients with no AXIOST™ stent implanted counted as failure for resolution of acute cholecystitis (AC) and censored at 60 days | 93.3% (28/30) [77.9%, 99.2%] | 100.0% (28/28) [87.7%, 100.0%] | | Days to resolution [97.8% 1-sided CI] | $5.30\pm14.90$ (30) (1.00, 60.00) [0.0, 10.78] | $1.39\pm0.92$ (28) (1.00, 5.00) [0.0, 1.74] | | Additional Analysis: Resolution of AC counted for all patients regardless of AXIOST™ stent implant | 100.0% (30/30) [88.4%, 100.0%] | 100.0% (28/28) [87.7%, 100.0%] | | Days to resolution [97.8% 1-sided CI] | $1.60\pm1.50$ (30) (1.00, 8.00) [0.0, 2.15] | $1.39\pm0.92$ (28) (1.00, 5.00) [0.0, 1.74] | | Secondary Effectiveness Endpoint | | | Table 3. Summary of Primary, Secondary, and Additional Endpoints for Clinical Study | Variable | ITT Patients (N=30) | Treated/PP Patients (N=28) | |-----------------------------------------------------------------------------------------------------|-----------------------------------|-----------------------------------| | Reintervention, migration, or occlusion [99.7% 1- sided CI] | 16.7% (5/30) [0.0%, 42.0%] | 14.3% (4/28) [0.0%, 40.2%] | | Additional Endpoints | | | | Technical success | | | | AXIOST™ stent placement: successful stent placement with confirmed stent patency | 93.3% (28/30) [77.9%, 99.2%] | 100.0% (28/28) [87.7%, 100.0%] | | AXIOST™ stent removal: successful endoscopic stent removal without stent removal-related SAEs | 100.0% (19/19) [82.4%, 100.0%] | 100.0% (19/19) [82.4%, 100.0%] | | Stent patency at stent removal visit | 100.0% (22/22) [84.6%, 100.0%] | 100.0% (22/22) [84.6%, 100.0%] | | Recurrence of acute cholecystitis symptoms | 10.0% (3/30) [2.1%, 26.5%] | 10.7% (3/28) [2.3%, 28.2%] | | Reintervention visit | 3.3% (1/30) [0.1%, 17.2%] | 3.6% (1/28) [0.1%, 18.3%] | | 72-hour post-stent removal visit | 0.0% (0/20) [0.0%, 16.8%] | 0.0% (0/20) [0.0%, 16.8%] | | Final study visit | 7.7% (2/26) [0.9%, 25.1%] | 8.3% (2/24) [1.0%, 27.0%] | {10}------------------------------------------------ | | $8.30\pm7.14 (30)$ | $8.64\pm7.28 (28)$ | |---------------------------------------------------------------------------------------|--------------------------------|--------------------------------| | Days hospitalized (between index procedure and stent removal visit / end of study) | (3.00, 38.00) [5.74, 10.86] | (3.00, 38.00) [5.95, 11.34] | Numbers are: mean±standard deviation (N) (min, max) [confidence interval] for continuous variables or % (count/sample size) [confidence interval] for binary variables. All confidence intervals are two-sided 95% unless otherwise specified. Primary Effectiveness Endpoint: For the Primary Analysis of the Primary Effectiveness Endpoint of Days to Resolutions of Acute Cholecystitis on the intend-to-treat (ITT) cohort (N=30), 2 ITT patients who did not receive an AXIOS stent were censored at 60 days as specified in the protocol. A mean ± standard deviation of days to resolution of 5.30±14.90 with a one-sided 97.8% confidence interval of [0.00, 10.78] was observed. Since the upper bound of the 97.8% confidence interval (10.78 days) was greater than the Performance Goal of 3.5 days, the null hypothesis that the mean days to resolution >3.5 days cannot be rejected and thus the endpoint has failed. The two patients who did not receive an AXIOS stent were followed until resolution of Acute Cholecystitis. We also evaluated the Primary Effectiveness Endpoint using the observed days to Acute Cholecystitis resolution regardless of AXIOS stent implantation. For this additional analysis, 1.60±1.50 days to resolution of Acute Cholecystitis for the 30 ITT patients with 97.8% one-sided confidence interval of [0.0, 2.15] was observed. Since the upper bound of the 97.8% confidence interval of the mean days to resolution of Acute Cholecystitis was 2.15 days. which is less than the Performance Goal of 3.5 days, this analysis rejects the null hypothesis in favor of the alternative hypothesis that days to resolution of Acute Cholecystitis is less than 3.5 days. For the treated/per-protocol cohorts (N=28), both the Primary and additional analyses vielded the same results of 1.39±0.92 days to resolution of Acute Cholecystitis (one-sided 97.8% confidence interval [0.0, 1.74]). Since the upper bound of the 97.8% confidence interval (1.74 days) is less than the Performance Goal of 3.5 days, the null hypothesis is rejected in favor of the alternative hypothesis that days to resolution of Acute Cholecystitis is <3.5 days. The different analyses for the primary effectiveness endpoint are summarized below: | Cohort Description | Time to Resolution of AC | Days to Resolution ± SD [97.8% CI] | |-----------------------|---------------------------------------------------------------------------------------------------------------------------|------------------------------------------| | 30 ITT subjects | As reported for 28 subjects who received AXIOS stent and 60 days for 2 subjects who did not receive the AXIOS stent | $5.30\pm14.90$ [0.00, 10.78] | | 30 ITT subjects | As reported for all 30 subjects | $1.60\pm1.50$ [0.0, 2.15] | # Table 1: Resolution of Acute Cholecystitis (AC) {11}------------------------------------------------ | 28 Treated/Per Protocol subjects | As reported for 28 subjects who received AXIOS stent | $1.39\pm0.92$ [0.0, 1.74] | |-------------------------------------|---------------------------------------------------------|------------------------------| |-------------------------------------|---------------------------------------------------------|------------------------------| #### Secondary Effectiveness Endpoint - Rate of re-interventions: There were 10 re-interventions in 8 patients. These re-interventions can be categorized as follows: - · 1 patient with one re-intervention not affecting the biliary tract - 2 patients with 2 re-interventions affecting the biliary tract for the management of . unrelated confirmed malignant biliary stenosis - 5 patients with 7 re-interventions affecting the biliary tract for reasons other than the . management of confirmed malignant biliary stenosis. Only the 7 re-interventions affecting the biliary tract for reasons other than confirmed malignant biliary stenosis were counted towards the Secondary Effectiveness Endpoint. The Secondary Effectiveness Endpoint of rate of reintervention including migration or occlusion was observed to be 16.7% (5/30) for ITT patients (one-sided 99.7% confidence interval [0.0, 42.0%]). The upper bound of the 99.7% confidence interval of rate of reintervention is 42.0%, which is less than the Performance Goal of 46.2%. Thus, for this analysis the null hypothesis is rejected in favor of the alternative hypothesis that the rate of reintervention is <46.2%. The treated and per-protocol cohorts had the same results for the Secondary Effectiveness Endpoint of 14.3% (4/28) of patients (one-sided 99.7% confidence interval [0.0, 40.2%]). The upper bound of the99.7% confidence interval of rate of reintervention is 40.2%, which is less than the Performance Goal of 46.2%. Thus, for this analysis the null hypothesis is rejected in favor of the alternative hypothesis that the rate of reintervention is <46.2%. #### Additional Endpoints Stent patency Stent patency was observed for 100% (22/22) of patients in whom patency was assessed at the Stent Removal visit. Technical stent placement success Technical stent placement was observed for 93.3% (28/30) patients. For two patients. the AXIOS™ stent could not be implanted successfully in the gallbladder as discussed in Section 3. Technical stent removal success Stent removal was attempted for 19 patients and was successful for all 19 thus technical stent removal success is 100% (19/19). Rate of recurrence of acute cholecystitis There were three cases of recurrence of acute cholecystitis, all cases were after resolution of the baseline acute cholecystitis and after removal of the AXIOS™ stent. One recurrent acute {12}------------------------------------------------ cholecystitis (0859G009) was identified during a reintervention for stone removal 15 days after AXIOSTM removal. One recurrent acute cholecystitis was reported at the final study visit 6 weeks after AXIOS™ removal and was managed with a cholecystectomy. The other recurrent acute cholecystitis case was reported 20 days after AXIOS™ stent removal and was associated with migration of plastics stents placed at the time of the AXIOSTM stent removal. This patient died one day later. Number of cumulative hospital and ICU days The mean ± standard deviation of the number of cumulative hospital days from the index procedure to the final study visit was 8.0±6.9 days. The number of ICU days was not collected. #### Adverse Events There have been no unanticipated adverse events (AEs) reported in this study. There have been 111 AEs of which 35 were recorded as SAEs. One SAE was reported as related to the AXIOS™ Stent and AXIOS™ Stent placement procedure. This event led to death. There were ten non-serious AEs related to the AXIOS Stent, stent placement procedure and/or stent removal. | Variable | All AEs | Related to AXIOS™ stent, AXIOS™ stent placement or removal procedure | |--------------------------------------------|----------------------------------|-------------------------------------------------------------------------------------| | Count | 111 | 11 | | % Subjects | 93.3% (28/30) | 30.0% (9/30) | | # AEs / Subjects | 3.7±3.0 (30) (0.0, 13.0) | 0.4±0.6 (30) (0.0, 2.0) | | Days to onset | 30.4±39.9 (111) (-6.0, 366.0) | 19.8±20.7 (11) (0.0, 56.0) | | Days to Resolution | 9.2±17.1 (68) (0.0, 84.0) | 4.7±6.3 (7) (0.0, 18.0) | | Visit when AE occurred | | | | Stent placement procedure | 3.6% (4/111) | 0.0% (0/11) | | Daily acute cholecystitis assessment visit | 24.3% (27/111) | 45.5% (5/11) | | Study stent removal | 11.7% (13/111) | 27.3% (3/11) | | 72-hour post-study stent removal visit | 0.9% (1/111) | 0.0% (0/11) | | Final study visit | 10.8% (12/111) | 0.0% (0/11) | | Reintervention visit | 2.7% (3/111) | 0.0% (0/11) | | Unscheduled visit | 45.9% (51/111) | 27.3% (3/11) | | Severity | | | | Mild | 59.5% (66/111) | 63.6% (7/11) | #### Table 4. Summary of Adverse Events {13}------------------------------------------------ | Moderate | 27.9% (31/111) | 27.3% (3/11) | |----------------|----------------|--------------| | Severe | 12.6% (14/111) | 9.1% (1/11) | | Unknown | 0.0% (0/111) | 0.0% (0/11) | | Serious Yes | 31.5% (35/111) | 9.1% (1/11) | The numbers in the table above are defined as follows: - % Subjects (Number of subjects with AEs/Number of subjects in ITT cohort) . - # AEs/Subjects (Min. Max) . - . Days to onset (Min. Max) - Days to Resolution (Min, Max) . - . Visit when AE occurred, Stent placement procedure, Serious (Number of AEs that occurred at that visit/Total number of AEs) There were four device-related AEs, with onset ranging from 20 days to 56 days after AXIOS stent placement. Three of these device-related AEs were non-serious and resolved without sequelae zero to 6 days after onset. One of the device-related AEs was serious and consisted of septic shock with onset 48 days after AXIOS stent placement, 28 days after AXIOS stent removal, and with fatal outcome one day after onset of septic shock. Details are provided below: - . Right Upper Quadrant Abdominal Pain (Subject 0305G006) - onset: 56 days after AXIOS stent placement; duration: 4 days; outcome: recovered/resolved. - Septic shock (Subject 0859G006) onset: 48 days after AXIOS stent placement; duration: . n/a; outcome: fatal. - . Sepsis (Subject 0859G007) - onset: 20 days after AXIOS stent placement; duration: 6 days; outcome: recovered/resolved. - Mucosal injury /minor bleeding (Subject 0859G009) onset: 35 days after AXIOS stent . placement; duration: 0 days; outcome: recovered/resolved. #### Conclusion The primary effectiveness endpoint consisted of the days to resolution of Acute Cholecystitis. The study hypothesized that this endpoint would be less than 3.5 days. The study observed 1.60±1.50 days to resolution of acute cholecystitis for the 30 ITT patients with 97.8% one-sided confidence interval of [0.0, 2.15], and thus met the study hypothesis. The secondary effectiveness endpoint consisted of rate of reinterventions affecting the biliary tract for reasons other than confirmed malignant biliary stenosis. The study hypothesized that this endpoint would be less than 46.2%. The study observed 16.7% (5/30) of patients with one-sided 99.7% confidence interval of [0.0, 42.0%], and thus met the study hypothesis. There have been no unanticipated adverse events (AEs) reported in this study. There have been one hundred eleven (11) AEs of which thirtv-five (35) were recorded as Serious Adverse Events (SAEs). Only one (1) SAE was reported as related to the AXIOS™ Stent and AXIOS™ Stent placement procedure; this event led to death. # META-ANALYSIS OF CLINICAL LITERATURE A systematic review and meta-analysis of the literature were conducted to provide an evaluation of available publications reporting on the rates of technical success, clinical success, recurrent cholecystitis, procedure-related adverse events, overall adverse events, and re-intervention in patients with acute cholecystitis who have undergone EUS-guided cholecystostomy with the {14}------------------------------------------------ AXIOS stent. Seventeen articles were retained for analysis, encompassing 713 patients, as summarized in Table 5 below. A random-effects model was utilized to account for heterogeneity in the analysis. | Outcome | AXIOS TM Gallbladder Random Effects Modelling | | | |-------------------------|--------------------------------------------------------|------------|------------------------------------------| | | # Refs | Total N | Meta-analysis Point Estimate (95% CI) | | Technical Success | 17 | 666 | 97.0% (95.1%, 98.5%) | | Clinical Success | 15 | 595 | 92.0% (89.2%, 94.3%) | | Recurrent Cholecystitis | 13 | 551 | 1.8% (0.4%, 4.2%) | | Procedure Related AEs | 14 | 591 | 12.0% (8.5%, 16.0%) | | Overall AEs | 16 | 610 | 22.7% (17.5%, 28.4%) | | Re-interventions | 5 | 257 | 10.3% (2.6%, 22.1%) | Table 5. Meta-Analysis of Data from Clinical Literature of AXIOS used for Gallbladder Drainage Notably, the metanalysis included a randomized control trial (Teoh AY, Kitano M, Itoi T, et al. Endosonography-guided gallbladder drainage versus percutaneous cholecystostomy in very high-risk surgical patients with acute cholecystitis: an international randomised multicentre controlled superiority trial (DRAC 1), Clinical Study, Gut, 2020;69(6):1085-1091), which compared endoscopic ultrasound (EUS-GBD) with the AXIOS stent versus percutaneous cholecystectomy (PT-GBD), the standard of care. This is the first prospective, multi-centered randomized controlled trial comparing EUS-GBD with PTGBD. After randomization of 80 patients and exclusion of a patient who developed gallbladder cancer, the analysis included 39 patients in the EUS-GBD group and 40 patients in the PT-GBD group. The following results were extracted from the literature for usage of LAMS (AXIOS) for management of acute cholecystitis: | Outcome | Study Reported Results (95% Confidence Interval) | |-------------------------|-----------------------------------------------------| | Technical Success | 97.4% (86.5%, 99.9%) | | Clinical Success | 92.3 % (79.1%, 98.4%) | | Recurrent Cholecystitis | 2.6% (0.1%, 13.5%) | {15}------------------------------------------------ | Procedure Related AEs | 12.8% (4.3%, 27.4%) | |-----------------------|-------------------------| | Overall AEs | 25.6% (13.0%, 42.1%) | | Re-interventions | 2.6% (0.1%, 13.5%) | There were no differences in technical success (97.4% vs 100%. p=0.494), clinical success (92.3% vs 92.5%, p=1), or 30-day mortality between EUS-GBD and PT-GBD (3/39 (7.7%) vs 4/40 (10%), p=0.675). Compared to PT-GBD, EUS-GBD significantly reduced 30-day adverse events (12.8% vs 47.5%, p=0.001) and 1-year adverse events (25.6% vs 77.5%, p<0.001). # Pediatric Extrapolation In this De Novo request, existing clinical data were not leveraged to support the use of the device in a pediatric patient population. # LABELING Physician labeling includes the device indications for use, a description of the device, warnings and precautions, clinical data on the device, and instructions for the safe and effective use of the device. The labeling satisfies the requirements of 21 CFR 801.109 Prescription devices. Per the Special Controls for this type of device, the labeling includes: - . Instructions for stent deployment, use, and removal - Information on device technical parameters . - A summary of clinical data obtained with the device, including a summary of reported . adverse events and a summary of subject demographics Other labeling includes an implant card and an information booklet for patients. #### RISKS TO HEALTH The table below identifies the risks to health that may be associated with use of the gallbladder drainage stent and delivery system and the measures necessary to mitigate these risks. | Risks to Health | Mitigation Measures | |----------------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------| | Procedural complications, leading to recurrent cholecystitis Improper stent placement Improper stent removal Stent obstruction/ingrowth Stent migration/dislodgement | Clinical performance data Non-clinical performance testing Labeling | {16}------------------------------------------------ | Tissue unable to support stent placement due to: - Lack of gallbladder wall integrity - Lack of gallbladder adherence to bowel wall | Clinical performance data Non-clinical performance testing Labeling | |-------------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------| | Infection/sepsis | Sterilization validation Labeling | | Adverse tissue reaction | Biocompatibility evaluation | | MR incompatibility, leading to tissue damage | Non-clinical performance testing | ## SPECIAL CONTROLS In combination with the general controls of the FD&C Act, the gallbladder drainage stent and delivery system is subject to the following special controls: - (1) Clinical performance data must demonstrate that the device performs as intended under its anticipated conditions of use, and capture any adverse events observed during clinical use. Data must describe major clinical outcomes including stent patency, stent placement, and stent removal. - (2) Non-clinical performance testing must demonstrate that the stent and any associated delivery systems perform as intended under anticipated conditions of use. The following performance characteristics must be tested to demonstrate the stent will withstand forces and conditions encountered during use: - Deployment testing of the stent under simulated use conditions; (i) - Removal force testing to demonstrate that the stent will remain in place: (ii) - Compression and expansion force testing; (iii) - (iv) Dimensional verification testing; - Tensile testing of joints and materials; (v) - Fatigue testing to characterize material strength; and (vi) - (vii) Corrosion testing. - The patient-contacting components of the device must be demonstrated to be (3) biocompatible. - (4) Performance data must demonstrate the sterility of patient-contacting components of the device. - Performance data must support the shelf life of the device by demonstrating continued (5) sterility, package integrity, and device functionality over the requested shelf life. - Performance data must evaluate the compatibility of the stent in a magnetic resonance (6) (MR) environment. {17}------------------------------------------------ - Labeling must include: (7) - Specific instructions and the expertise needed for the safe use of the device. (i) including deployment of the device, maintenance of the drainage lumen, and removal of the device: - (ii) A detailed summary of the clinical data pertinent to use of the device, including device- and procedure-related complications: - (iii) A detailed summary of the device technical parameters; and - (iv) An expiration date or shelf life. ## BENEFIT-RISK DETERMINATION The probable risks of the device for this intended use are based on data collected in the clinical study described above. The study identified 111 AEs, 35 of which are denoted as severe adverse events. The study noted that 16.7% of patients required reintervention. These adverse events were not unexpected given the high-risk patient population (i.e., those too ill to undergo cholecystectomy) and were comparable to what is observed for the clinical alternative. percutaneous cholecystostomy. There were no unanticipated AEs reported in this study. There were 111 AEs of which 35 were recorded as SAEs. Only one SAE was reported as related to the AXIOS Stent and AXIOS Stent placement procedure. This event led to death (see narrative below). There were ten non-serious AEs related to the AXIOS Stent, stent placement procedure and/or stent removal. The device related SAE occurred after successful stent removal, with persistent debris in the gallbladder and loss of plastic stents to maintain drainage. There were 10 re-interventions in 8 patients. Below is a narrative for the serious AE of 'septic shock' in Subject 0859G006: The patient's baseline medical history was notable for atrial fibrillation, secondary heart failure with preserved ejection fraction, chronic renal failure KDIGO 4 with a clearance of 17 and acute cholecystitis (calculous, Grade 1). The subject underwent the AXIOS™ stent 0859G006 placement procedure into the gallbladder using a transgastric approach on 23FEB2021. Stone removal was performed. and drainage was visualized through the study stent. It was confirmed on 26FEB2021 that the acute cholecystitis had resolved. The study stent was removed on 23MAR2021, and a mucosal injury was noted (linear ulceration of the greater curvature of the stomach). Stone and food debris removal was also performed from the gallbladder during the AXIOS™ stent removal procedure. A small sessile gallbladder polyp measuring +/-3-4mm was visualized and biopsied. Two (2) Solus plastic double pigtail stents (10 Fr x 5 cm) were placed in the gallbladder through the fistula tract after the AXIOS™ stent removal to prevent recurrence of food rests accumulating in the gallbladder. The patient was hospitalized on 12APR2021 with right hypochondrium pain. Augmentin was started. Abdominal US showed minimally thickened gallbladder wall, trace fluid in the gallbladder bed, and the gallbladder was filled with sludge/ food residue suggestive of cholecystitis. The 2 Solus plastic stents that were placed on 23MAR2021 were not visible. The patient developed shock, hypotension, reduced awareness (GCS 12/15) and required oxygen (up to 5L ). At the time of admission, patient had no fever, a white cell count of 11. 7 x 10*12 and a CRP level of 27.9mg/dL. The CRP rose to 280mg/dL the next day. Subject was considered to be septic in view of clinical presentation and CRP was elevated at 280 mg/L. Patient went into cardiac arrest and thoracic massage was started. After 20 minutes of cardiopulmonary resuscitation, a decision was made to stop the thoracic massage. The {18}------------------------------------------------ subject expired on (b)(6) as a result of cardiac arrest and presumed septic shock possibly from recurrent acute cholecystitis. The Secondary Effectiveness Endpoint of rate of reintervention including migration or occlusion was observed to be 16.7% (5/30) for ITT patients (one-sided 99.7% confidence interval [0.0, 42.0%1). The probable benefits of the device are also based on data collected in the clinical study and the literature analysis. The clinical study demonstrated that the device could assist in resolving symptoms associated with AC. The clinical study also helped demonstrate proper stent placement and removal. 28 of the 30 natients in the ITT cohort achieved technical success (93.3%), i.e., underwent successful placement of the AXIOS stent with subsequent resolution of cholecystitis within 1.39±0.92 days (one-sided 97.8% CI [0.0, 1.74] days). Two of the 30 patients in the ITT cohort did not receive the AXIOS stent and accordingly underwent alternate treatment for their AC, namely using antibiotics in one patient fresolved at day 1] and percutaneous drainage in the other [resolved at day 8]. However, a potential limitation of this study is the lack of any comparator and the limited sample size (N=28 per protocol patients). In addition, placement of the device requires a skilled interventional endoscopist and the procedure is operator dependent. In the available clinical literature, a recent randomized clinical trial (Teoh AY, Kitano M, Itoi T, et al. Endosonography-guided gallbladder drainage versus percutaneous cholecystostomy in very high-risk surgical patients with acute cholecystitis: an international randomized multicenter controlled superiority trial (DRAC 1), Clinical Study, Gut. 2020;69(6):1085-1091.) compared gallbladder drainage with the AXIOS stent versus percutaneous cholecystostomy, a standard of care procedure. The study data noted that patients treated with the AXIOS stent experienced fewer 30-day and 1-year adverse events than patients treated with the standard of care. For patients treated with the AXIOS stent, 1 year adverse events were fewer (10 (25.6%) versus 31 (77.5%) p<0.001); as were 30-day adverse events (5 (12.8%) versus 19 (47.5%), p=0.010), reinterventions after 30 days (1/39 (2.6%) versus 12/40 (30%), p=0.001), the number of unplanned readmissions (6/39 (15.4%) versus 20/40 (50%), p=0.002) and recurrent cholecystits (1/39 (2.6%) versus 8/40 (20%), p=0.029). Postprocedural pain scores and analgesic requirements were also less (p=0.034). The technical success (97.4% versus 100%, p=0.494), clinical success (92.3% versus 92.5%. p=1), and 30-day mortality (7.7% versus 10%, p=1) were statistically similar. This randomized trial with the standard of care comparator provides strong real-world evidence of the performance of the device. AC is recognized as a morbid condition among patients who cannot undergo curative treatment by surgical cholecystectomy. When compared to other treatment options (e.g., percutaneous cholecystostomy), transluminal drainage is a less invasive procedure with a favorable benefit risk profile outlined by the study above. Clinical success (based on resolution of AC symptom) is likely cofounded by the morbid condition of the patients. Nonetheless, the provided clinical data were able to show a resolution of symptoms for the per protocol patient population. Moreover, the trial data demonstrate technical success, including a proper stent placement, patency, and removal. {19}------------------------------------------------ ## Patient Perspectives This submission did not include specific information on patient perspectives for this device. #### Benefit/Risk Conclusion In conclusion, given the available information above, for the following indication statement: The AXIOS Stent and Electrocautery Enhanced Delivery System is indicated for use to facilitate transgastric or transduodenal endoscopic drainage of the gallbladder in patients with acute cholecystitis who are at high risk for surgery. The probable benefits outweigh the probable risks for the AXIOS Stent and Electrocautery-Enhanced Delivery System (10 mm x 10 mm Stent); AXIOS Stent and Electrocautery-Enhanced Delivery System (15 mm x 10 mm Stent). The device provides benefits, and the risks can be mitigated using general controls and the identified special controls. #### CONCLUSION The De Novo request for the AXIOS Stent and Electrocautery-Enhanced Delivery System (10 mm x 10 mm Stent); AXIOS Stent and Electrocautery-Enhanced Delivery System (15 mm x 10 mm Stent) is granted and the device is classified under the following: Product Code: OXH Device Type: Gallbladder drainage stent and delivery system Regulation Number: 21 CFR 876.5016 Class: II

AXIOS Stent and Electrocautery-Enhanced Delivery System (10mm x 10mm Stent); AXIOS Stent and Electrocautery-Enhanced Delivery System (15mm x 10mm Stent)

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AXIOS Stent and Electrocautery-Enhanced Delivery System (10mm x 10mm Stent); AXIOS Stent and Electrocautery-Enhanced Delivery System (15mm x 10mm Stent)

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